The role of cytochromes P-450 in cyclosporine metabolism.
In most patients, the rate-limiting step in the elimination of cyclosporine from the body is its conversion to metabolites by cytochrome P-450 IIIA enzymes in the liver and, possibly, intestine. The significant differences found among patients in the daily dose of cyclosporine required to attain target blood levels has been attributed directly to corresponding interpatient differences in the catalytic activities of P-450 IIIA enzymes. Competitive inhibition or induction of P-450 IIIA activity appears to explain most of the clinically significant interactions of drugs with cyclosporine metabolism that have been reported. The critical importance of P-450 IIIA in the body's handling of cyclosporine has made it possible to identify potential drug interactions before they are reported. Future investigations in this field are likely to result in reduction in the cost and toxicity associated with cyclosporine therapy.
Watkins
P B
PB
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109.
D003524:Cyclosporins / Q000378:metabolism* / Q000493:pharmacokinetics; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004347:Drug Interactions; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008099:Liver / Q000378:metabolism
D003524:Cyclosporins; D003577:Cytochrome P-450 Enzyme System